The primary goal of these studies is an understanding of the short-term regulation of tyrosine hydroxylase in the central nervous system. We have previously shown an activation of the soluble enzyme (via a decrease in the apparent Km for the reduced pterin cofactor) by phosphorylation or catecholamine removal by G-25 chromatography in striatum, adrenal gland and hypothalamus. We have also shown that phosphorylation results in a significant reduction in K, for dopamine and release from end-product inhibition as its primary means of tyrosine hydroxylase activation. The data suggests that this mechanism could be operative in vivo at physiological concentration of dopamine.